The unprecedented growth in number of persons over 65 yrs of age will place an increasing percentage of our population at risk for poor health. It has been suggested that this increased risk can be explained in part by the aging organisms' blunted ability to adapt to internal or external stress. That is, aging may be characterized by a general decline in the ability to maintain homeostasis. One such homeostatic response is the ability to maintain homeothermy which is compromised in older cold-exposed humans and rodents. Of special interest is the observation that this effect of age appears to be more pronounced in males than in females (in humans and in rats). Thus, the effect of aging on the ability to maintain homeothermy in particular and homeostasis in general may be gender dependent. Our study of thermoregulatory function in aging rats will provide a model by which we will gain a clearer understanding of these effects of aging and gender on homeostasis. A major objective of this project is to evaluate the physiological/biochemical basis for the attenuated effectiveness of thermoregulatory responses in older male/female rats. As a model system for studying the aging/gender effects on homeostatic alterations, we will use brown adipose tissue (BAT) for which we have demonstrated blunted thermogenic responses in older vs younger males and in older males vs their female counterparts. Since BAT function is regulated by the sympathetic nervous system and modulated by several hormones, our proposal examines the Interaction of gender and aging on BAT thermogenic capacity (uncoupling protein), adrenergic receptors, signal transduction, substrate availability and mobilization, availability of insulin and thyroid hormone, and sensitivity to Insulin. We will also examine possible alterations in skeletal muscle, whose thermogenesis may also be attenuated in aging animals. Procedures include membrane and cell isolations, Scatchard plot analysis, immunobinding, in vitro and in vivo uptake of 2-deoxyglucose, radioimmunoassays, euglycemic clamp, hindlimb perfusion, and variety of enzyme assays. These studies should provide considerable insight into gender/aging interactions relevant to neural and hormonal modulation of metabolic regulation, thermoregulation, and homeostatic maintenance.